Osteoarthritis (OA) at the knee is a leading cause of chronic disability. Knee OA that progresses beyond mild stages is responsible for much of the cost of knee OA as a whole. Few strategies to prevent knee OA disease progression or OA-related disability exist, in large part due to limited knowledge of factors responsible for these outcomes. In recent years, there has been a shift in epidemiological studies to concentrate more on OA progression than on initial OA development. Also, there is a growing recognition of the role played by local factors. Knee stability is crucial both to daily activity performance and to protection of the joint against damage during activity. Knee instability encompasses a spectrum of symptoms and measurable phenomena, which may bear little relation to each other, including low confidence in the knees, episodes of buckling or giving way, and excessive motion at the knee in a specific plane. In this application, we propose to examine the effect of low knee confidence, low confidence that the knee will not buckle, higher buckling frequency, and excessive frontal plane motion during gait at baseline on baseline-to-two-year physical function decline and cartilage loss by MRI in persons with knee OA. To maximize efficiency and reduce the budget, this study builds off the knee OA natural history study recently funded within the competing renewal of our Multidisciplinary Clinical Research Center (MCRC) grant. Through the MCRC project, which focuses on hip muscle parameters and has no assessment of dynamic instability, baseline and two-year evaluations of a cohort with knee OA are already funded (including the covariate and outcome data the proposed study requires). We now request funding to add the assessments of dynamic instability symptoms and measures and to test the hypotheses relating these measures to joint-level and person-level outcomes. The proposed project also represents a competing renewal application, building upon and extending our results from the ongoing RO1 cycle. Results from the proposed study will inform development of physical and rehabilitative therapy for knee OA that might target specific aspects of dynamic instability. This is a key, modifiable component of the knee joint environment that has received little attention, despite a potentially large role of dynamic instability in the preservation of knee joint integrity and person-level functioning. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) at the knee is a major cause of disability. Few strategies to prevent OA disease progression or OA-related function decline exist. We propose to examine the effect of knee confidence, confidence that the knee will not buckle, frequency of buckling episodes, and instability measured during quantitative gait analysis on joint cartilage loss and physical function decline in a cohort of persons with knee OA. Results from the proposed study will aid development of physical and rehabilitative therapy for knee OA that might target specific aspects of dynamic instability. This is a key, modifiable component of the knee joint environment that has received little attention in knee OA, despite a potentially large role for stability in the preservation of knee joint integrity and person-level functioning.